CircZCCHC2 decreases pirarubicin sensitivity and promotes triple-negative breast cancer development via the miR-1200/TPR axis.

ABSTRACT

Triple-negative breast cancer (TNBC) has attracted attention due to its poor prognosis and limited treatment options. The mechanisms underlying the association between circular RNAs (circRNAs) and the occurrence and development of TNBC remain unclear. CircZCCHC2 is observed to be upregulated in TNBC cells, tissues, and plasma exosomes. Knockdown of circZCCHC2 inhibited the proliferation, migration, invasion, and epithelial-mesenchymal transition of TNBC cells in vitro and in vivo. Pirarubicin (THP) treatment downregulated circZCCHC2, and circZCCHC2 affected the sensitivity to THP. CircZCCHC2/miR-1200/translocated promoter region, the nuclear basket protein (TPR) pathway was cascaded and verified. It is demonstrated that circZCCHC2 plays a crucial role in the malignant progression of TNBC via the miR-1200/TPR axis, thereby activating the RAS-RAF-MEK-ERK pathway. The present results indicate that circZCCHC2 has the potential to serve as a novel prognostic biomarker for TNBC.